PROJECT SUMMARY Over the last four decades, biological and chemical modifiers have increased agricultural production in the US. Most US dairy producers administer sub-therapeutic, prophylactic doses of antimicrobials to their cows to enhance animal growth and prevent communal infectious diseases. This antimicrobial use risks the emergence of transmissible antibiotic-resistant bacteria in cows that can spread to dairy farmers via occupational exposure. We propose to define and compare the nasal microbiomes, gut microbiomes, and antimicrobial resistance genes of dairy workers and their cows to investigate potential harmful or beneficial effects on dairy farmers. Our proposal?s rationale is that occupational exposure of dairy farm workers to antimicrobial resistance genes and transmissible resistant bacteria via dairy cows is unknown. Our proposal?s central motivation is to understand the potential harmful or beneficial effects of dairy farm exposure on dairy farmers. Guided by strong preliminary data, this proposal pursues four aims. In aim one, we will characterize the nasal and gut microbiomes of dairy cows, dairy farmers, and office workers, testing the hypothesis that dairy farmers and dairy cows have a shared microbiome composition that differs from office workers? microbiome composition. In aim two, we will quantitatively assess temporal changes in microbial communities, virulence factors, and resistomes between dairy cows and dairy farmers and develop computational models to identify risk factors associated with seasonal influenza and gastrointestinal symptoms, testing the hypothesis that nasal and fecal communities of dairy cows and dairy farmers will share resistance genes and virulence factors. In aim three, we will understand and predict the temporal transmission dynamics of antimicrobial resistance genes between dairy cows and dairy farmers, testing the hypothesis that antibiotic resistance genes present in dairy cows will be reflected in dairy farmers they are in contact with. In aim four we will understand the conception and behaviors of dairy farmers regarding the shared dairy cow and dairy farmer microbiome, testing the hypothesis that dairy farmers have incomplete knowledge of the occupational hazard posed by antimicrobial resistant organisms, but are willing to learn about these risks and take steps to mitigate them. Our proposal is innovative with its involvement of a cross-disciplinary team of researchers to focus state-of-the- art tools on the understudied public health problem of dairy cow to dairy farmer antimicrobial resistant organism transmission. Our proposal is significant because it will 1) improve our understanding of shared vs unique components of microbiome and resistome between dairy cows, dairy farmers and office workers, 2) enhance our knowledge on the impact of current use practices in dairy industry on AMR transmission and its potential risk to farm workers. Our proposal is impactful because it will provide specific avenues for communication of risk mitigation strategies to dairy farmers to reduce transmission of antibiotic resistant organisms and it will provide a general template for other agricultural livestock-worker combinations.